Neisseria

Family Neisseriaceae with four genera:

1. Neisseria gonorrhoeae, N.meningitidis

2. Moraxella catarrhalis
3. Acinetobacter baumannii, lwoffii
4. Kingela kingii

To be covered:
1. Neisseria genus
- Definition
- History
- Classification, Identification
 -Characteristics
2. N.meningitidis
(i) pathogenesis
(ii) epidemiology
(iii) laboratory diagnosis
(iv) treatment
(v) Prevention and control
3. N.gonorrhoeae
(i) Pathogenesis
(ii) Epidemiology
(iii) Laboratory diagnosis
(iv) Treatment
(v) Prevention and control
4.Other Neisseriae
5.M.catarrhalis
Definitions:
Neisseriae are gram-ve cocci that usually occur in
pairs as coffee bean shaped; are strictly aerobic
and are oxidase + ve.
Two main pathogenic species for man:
N.gonorrhoeae (gonococcus) and N.meningitidis
(meningoccocus)

Typically occur intracellularly within

polymorphonuclear cells.
Other Neisseria Sp. are normal residents in human
respiratory tract and do not normally cause disease.

Gonococcus and meningococcus have 70% DNA

homology and are distinguished by few laboratory
tests.
 Characteristics of Neisseria

Physical Morphology:
– Bacterial cell approximately 1um diameter, non
motile, non spore forming
– Pathogenic forms occur intracellularly in neutrophils
– Abnormal forms may occur after exposure to
antibiotics esp. cell wall active ones e.g. penicillin.
– N.meningitidis and N.gonorrhoeae cultures autolyse
rapidly on exposure to cold, drying, sunlight, and
alkaline environments
– Pathogenic Neisseria require enriched media
supplemented with serum or other animal proteins
such as Casein hydrolysates, vitamins and
haemoglobin
On culture:
Form characteristic convex, shiny, mucoid (viscous)
colonies approximately 2mm in diameter after 24 hours
incubation depending on quality of media.
The colonies usually are colour less or yellowish brown in
colour.
Neisseria prefer a moist (humid) growth environment
with 2.5-10% Co2 e.g. in a Candle jar containing a wet
blotting paper or cloth at the bottom
Neisseria produce Oxidase enzymes (Oxidase +ve)
Meningococcus constitutes part of normal upper respiratory
tract flora of man

Virulent forms cause:

- pyogenic meningitis &
meningocaemia

Gonococcus – causes Genital discharge (Gonorrhoea)

- Conjunctivitis
- Disseminated disease (septicaemia)
- Found in asymptomatic carriers
History:
Venereal urethritis – ancient disease
- In old testament, book of Leviticus
- Hippocrates (Father of Medicine)
4th & 5th century BC
- Galen, 2nd Cent. AD coined term
gonorrhoea-”flow of seed” confused
with flow of semen in males
- Albert Neisser 1879 described bacterium
Neisseria
- Leistikow & Loeffler first to culture (grow)
the gonococcus in 1882
`
Table 1 Biochemical reactions of the Neisseriae

ACID Formed From

Species Glucose Maltose Lactose Sucrose DNase
Growth on or
MTM, ML, Fructose
or Nyc
Medim
N.gonorrhoeae + + - - - -
N.meningitidis + + + - - -
N lactamica + + + + - -
M sicca - + + - + -
N mucosa - + + - + -
N flavescens - + + - + -
N.cinerea - - - - - -
M catarrhalis + - - - - +

.MTM=modified Thayer-Martin medium, ML=Martin-Lewis Medium,

NYC=New York City medium
2. N.meningitidis
Probably the second or third commonest cause of pyogenic (purulent)
meningitis in E.Africa in non-HIV infected individuals
Other causes of acute pyogenic meningitis (aetiologies) being :
– D.pneumoniae
– H.influenzae (infants and children < 5 years)
– Streptococci incl. S.agalactiae in neonates
– Coliforms and Pseudomonas.
– C.neoformans, a fungal yeast is the commonest cause of HIV
associated meningitis.
– N. meningitidis can be serogrouped by polysaccharide antigen
agglutination tests into groups A, B, C, D, X, Y, Z, W135.
– Most epidemics of meningococcal disease are due to sero
groups A, B, C or Y & W135
– Outbreaks in the so called Cerebral Spinal Meningitis belt in
Africa lying between
South of Sahara and the Equator occur regularly and are
mostly due to sero group A meningococcus; epidemics
occur from time to time due to lowered body immunity.
Occur during dry and cold night seasons especially among:
- People crowded in small poorly ventilated dwellings
- mass migrations is a factor
- Sero group A is the predominant cause of epidemics
(small) which have occurred in Tanzania.
A antigen = polymer of N-acetyl-0-acetyl mannosamine
phosphate
C antigen = N-acetyl-o-acetylneuraminic acid
Pathogenesis of N.meningitidis:
- Humans are the only natural hosts
- Found as normal flora and portal of entry is the
nasopharynx into blood stream leading to
meningococcaemia with high fever and haemorrhagic
rash which may be severe the so called Waterhouse-
Friderichsen syndrome characterized by:
– Septicaemia
– Disseminated intravascular coagulation
– Circulatory collapse
– Meningitis (purulent) is the commonest
complication of meningococcaemia
Epidemiology:
- Occur in epidemic waves
- 5-30% of normal population may harbour meningococci
in the nasopharynx during non epidemic seasons
- During outbreaks carrier rate may go up to 70-80%.
- Epidemics are usually preceded by rise in carriers.
- Occur in overcrowded environments e.g among
refugees and pilgrims
– Outer membrane or meningococcus divided into classes
1,2 and 3 similar to Por-proteins of gonococcus and
contribute to up to 20 serotypes.
– Serotypes 2 & 15 have been associated with epidemics
Prevention:
1. Avoidance of overcrowding and ensuring adequate
ventilation
2. Immunization in selected groups of individuals
– Vaccines against Sero group A, C, Y & W 135
polysaccharide are available either singly or in
different combinations ; may not be effective in
children below 2 years old
– For group B meningococcus a mixture of
polysaccharide and protein antigens are used as
vaccines in many countries in Europe & the USA.
– Vaccines may not prevent the carrier status.
3. Chemoprophylaxis – Rifampicin e.g. 600 mg b.d. in
adults orally for 2 days to close household contacts
may be effective if available.

4. Treatment:
- Benzyl penicillin in high doses is drug of choice
- Sulphonamides – 5-15% noted to be resistant to
this drug hence may not work.
- Chloramphenicol in those allergic to penicillin
- 3rd generation cephalosporins such as ceftriaxone or
cefotaxime if available may also be effective.
3.Neisseria Structure

N.gonorrhoeae
• Table 21-3 Antigenic heterogeneity of Neisseria gonorrhoeae

Antigen Number of Types

Pillin Hundreds
Por (protein’ (US System)(Protein Por A with 18 subtypes
1) Por B with 28 subtypes
Opa (protein II) Many (perhaps hundreds)
RMP (protein III) One
Lipooligosaccharide Eight or more
Fbp (iron-binding protein) One
Lip (H8) One
IgA1 protease Two
N.gonorrhoeae
The gonococcus usually has no polysaccharide capsule
compared with the meningococcus which has;
capsule can be demonstrated by negative staining.

Pathogenesis of N.gonorrhoeae:
- Attach mucus membranes of genitalia, eye, throat,
rectum → acute suppuration → chronic inflammation →
fibrosis or scar formation leading to stricture of urethra,
fallopian tubes or epididymis.
Pathogenesis of N.gonorrhoeae contd:
- In ♂, starts with anterior urethritis
- yellow, creamy pus, dysuria ;may ascend to
prostate → epididymis & lead to urethral stricture and
stricture of epididymis leading to infertility.
- In males infection may occasionally be asymptomatic.

- In ♀ → Infection involve posterior fornix and cervix

→mucopurulent discharge →may involve rectum in
proximity (proctitis).
From cervix → uterus and fallopian tubes (salpingitis)
& tubo-ovarian abscess (Pelvic inflammatory disease –
PID)
- May be complicated by infertility due to stricture of the
fallopian tubes.
Pathogenesis contd
– In the 60s and 70s up to 50% of women had
secondary infertility by age 30 years due to tubal
blockage resulting from repeated STIs including
gonorrhoea
– Infection in females mostly asymptomatic compared
with infection in males where most are symptomatic .
– In the 70s & 80s up to 10-20% of young adult
females were infected asymptomatically.
– Currently approximately 2-4% of adult females are
infected
– In both sexes the gonococcus may spread to blood
stream, skin, joints, eyes & even meninges.
– In newborns acquisition during vaginal delivery may
lead to severe purulent conjunctivitis (Ophthalmia
neonatorum) leading to blindness if untreated.
– This may be prevented by prophylaxis with antibiotic
eye ointment e.g. erythromycin.
Treatment:
Penicillin in high doses as a single dose used for treatment until early 1980s after which
appearance of B-lactamase +ve strains first
reported in 1976
in Liverpool, U.K.
– In 1982 reported the first penicillinase producing strain in TZ
in (MNH); soon precluded use of penicillin when more than 5% resistance
appeared.
- Penicillin is no longer in use for treatment of gonorrhoea

Currently Drugs of 1st Choice for gonorrhoea:

Ciprofloxacin as a single oral dose 400mg or Ceftriaxone inj.; In adults; 250 mg im.
Resistance to quinolones is spreading in the world and may already entered Tanzania
In the USA quinolones are no longer recommended for gonorrhoea
Single dose of Azithromycin oral treatement may replace ciprofloxacin
Spectinomycin as a single 2gm injection may also be effective in adults as second
line treatment.
Ophthalmia in neonates can be treated with parenteral treatment with ceftriaxone inj.
Epidemiology of N.gonorrhoeae infections:
• Human hosts are the reservoir
– Primarily spread through unprotected sex with
asymptomatic carriers or from? symptomatic ones
who cannot avoid sex
Risk of infection from ♀→♂ =20-30%
Opposite ♂ to ♀ risk much higher.
– Mother to child during delivery → ophthalmia
– Antoinoculation to eyes with hands in men under
unhygienic conditions following milking of urethra not
followed by handwashing.
Epidemiology contd.
– Close contact with contaminated towels.

Prevention and Control

1. Avoiding multiple sexual partners
2. Early detection and treatment of index cases and
their contacts
3. Screening of high risk groups esp. asymptomatic ♀
4. Promote safe sex including use of condoms;
Consistent correct condom use >90% effective
5. Prophylaxis with erythromycin eye ointment against
neonatal ophthalmia
6. Implement National STI control programme
 4.Other Neisseriae

The other Nisseria sp. rarely cause disease

in man but may grow on selective media
used to isolate N.meningitidis or
N.gonorrhoeae and be confused with
these e.g.N.lactamica is found in 3-40% of
swabs from nasopharynx
Unlike other Neisseria it ferments lactose
 5.M.catarrhalis
• Previously called Branhamella catarrhalis and before
N.flavescens
• Normal flora on nasopharynx in 40-50% in school
children
• Causes bronchitis, pneumonia, sinusitis, otitis media and
conjunctivitis.
• Most isolates from disease conditions produce Beta
lactamase
• Associated with infections in immunodeficient patients
• Non fermentative and produces DNAse
• Produces butyrate esterase ,a basis for fluorometric test
for identification